It is known that bioactive polypeptides or their derivatives exhibit a variety of pharmacologic activities in vivo. Some of these polypeptides have been produced on a large scale by utilizing Escherichia coli, yeasts, animal cells or host animals such as hamsters using recently developed genetic engineering and cell technology, and put to medicinal use. However, these bioactive polypeptides must be frequently administered because of the generally short biological half-life. The repeated injections takes a significant physical burden on patients. To overcome this disadvantage, various attempts have been made to develop sustained-release preparations comprising bioactive polypeptides.
EP-461630 discloses prior art production technologies for sustained-release preparations designed for the enhanced efficiency of entrapment of water-soluble bioactive peptides. These preparations are obtained from an oil/water (o/w) emulsion comprising dissolving a water-soluble bioactive polypeptide, a biodegradable polymer and a fatty acid salt in an organic solvent.
Although various attempts have been made to produce a sustained-release preparation retaining the bioactivity of bioactive polypeptides as mentioned above, there has not been a clinically satisfactory sustained-release preparation with efficiencient entrapment of a bioactive polypeptide into a biodegradable polymer, and suppression of initial drug burst, constant long-term drug release, and so on.